It should be
remembered that the World Health Organisation criteria for
osteoporosis and osteopenia were developed for women and may or may not
apply to children. Risk and preventive factors for low bone mass and
osteoporosis in children are considered in Chapter
1.

7a. Corticosteroid
use is a well known cause of osteoporosis in children. High dose
methotrexate (such as used for childhood leukaemia) causes osteopathy
in children and cyclosporine has been shown to cause a high
turnover osteopenia. Active arthritis has osteopenic effects around
affected joints and decreases bone density away from affected jointsi.

7b. At
diagnosis of childhood malignancy, there were no differences in BMD
compared to healthy age- and gender-matched controls. However, increased
bone resorption and decreased bone formation was already present. The
negative balance in bone turnover decreased throughout the follow-up and a
reduction in BMD was observed 6 months after diagnosis. No independent
correlation was found between the reduction in BMD and corticosteroid
therapy or any of the antineoplastic agentsi.

7c. The
cause of idiopathic juvenile osteoporosis is unknown. The basic
strategy of treatment is to protect the spine until remission occurs. Sex
steroids are contraindicated. Bisphosphonates, calcitriol, fluoride and
calcitonin have been administered therapeutically but the results were
equivocal. Usually the disease remits by itselfi.

7d.
Speed of sound (SOS) shows a significant correlation with BMD as
measured by DXA, albeit with wide 95% confidence intervals in a small
pilot study. Quantitative ultrasound (QUS) was also well tolerated and was
technically easy to perform. With the added advantage that it is free from
radiation risk, further assessment of this potentially valuable tool
for measuring bone status in children is warrantedi.
See also Chapter 2 for a consideration of DXA versus ultrasound in adults.

7e. There
is evidence that some children with rheumatic disease receiving
corticosteroids would benefit from calcium and vitamin D
supplementation. During supplementation, of nine patients who
completed all the BMD measurements, the mean spinal BMD increased to 11%
over the baseline measures. Eight patients had increased BMD and one had
decreased BMD. Seven patients had lower BMD values without
supplementation, two had improved valuesi.

Calcitriol has
also been used in idiopathic juvenile osteoporosis with improvement in
symptoms, fracture frequency and bone mineral content. Follow-up at 6 and
12 months showed a significant increase in bone mineralisation, which
reached normal values in two children after 12 months of treatment. The
untreated patient did not show an improvement of bone mineralisation in
the same timeii.

Although there is little evidence that calcium and vitamin D
supplementation is of benefit in childhood osteoporosis, it is recommended
that such children should receive an adequate calcium intake(see
Statement 1.2e).

ii. Saggese G, Bertelloni S,
Baroncelli GI, Perri G, Calderazzi A. Mineral metabolism and calcitriol
therapy in idiopathic juvenile osteoporosis. American Journal of
Diseases of Childhood 1991; 145: 457-462(Type IV evidence – case
studies of four children ranging in age from 2.3 to 12.6. Three children
were treated with calcitriol (1,25—dihydroxycholecalciferol) (0.50
microg/day in two and 0.25 microg/day in the other). The fourth patient
was not treated because of parental refusal)

7f. Alendronate
has a positive effect on secondary osteopenia/osteoporosis in children
with connective tissue diseases. BMD increased by a mean ± SD of 14.9 ±
9.8% (p<0.002 versus baseline) in the treated patients (reaching the
normal range in 13 patients), while the BMD was 2.6 ± 5% (not significant
versus baseline) in the control group (15 had a decrease). There was a
large increase in BMD (15.3 ± 9.9%) after alendronate therapy in the 16
children who had their BMD followed up in the year before the study,
during which time they had shown little increase in BMD (1.03 ± 6.3%),
and often a decrease. No new fractures were observed after alendronate
therapy was initiatedi.

i. Bianchi ML, Cimaz
R, Bardare M et al. Efficacy and safety of alendronate for the
treatment of osteoporosis in diffuse connective tissue diseases in
children: A prospective multicenter study. Arthritis & Rheumatism 2000;
43(9): 1960-1966(Type III evidence – controlled study
of 38 children with low bone mass treated with alendronate (5 mg/day for a
body weight of ≤20
kg; 10 mg/day for >20 kg). 38 children who had the same primary
disorders as the study patients but in a less severe form, served as
untreated control patients)

7g. Intravenous
pamidronate appears to be a useful therapeutic option in childhood
osteoporosis, but its use in children must still be regarded as
experimental and therefore closely monitored. Each child had rapid
pain relief following the first treatment, followed by large increments in
lumbar spine bone density over one year (%increments of 26%-54% as
compared to the expected increases due to growth of 3%-15%)i.Caveat: This is
not a licensed indication. Oral pamidronate is not used anymore and is not
available.

i. Shaw NJ, Boivin
CM, Crabtree NJ. Intravenous pamidronate in juvenile osteoporosis. Archives
of Disease in Childhood 2000; 83(2): 143-145(Type IV evidence – case
studies of five children with vertebral osteoporosis who developed
compression fratures in the thoracic and/or lumbar spine as a consequence
of five different conditions. Children received treatment with intravenous
pamidronate in doses ranging from 0.5-12 mg/kg/year)

7h. In children with
severe osteogenesis imperfecta, cyclic administration of
intravenous pamidronate improved clinical outcomes, reduced bone
resorption and increased bone density. The mean incidence of
radiologically confirmed fractures decreased by 1.7 per year (p<0.001)
but treatment did not alter the rate of fracture healing, the growth rate
or the appearance of growth plates. Mobility and ambulation improved in 16
children and remained unchanged in the other 14. All children reported
substantial relief of chronic pain and fatigue. 26 children experienced an
‘acute-phase reaction’ on the second day of the first infusion cycle;
this was controlled with acetaminophen and did not recur during subsequent
treatment cyclesi.

7i. Bisphosphonates
offer the pediatrician a new tool to treat children with primary and
secondary metabolic diseases associated with increased bone resorptioni
and their use in paediatrics is sure to increaseii. As more
children receive these drugs for an expanding range of conditions, very
detailed patient monitoring is critical and these children should be
followed up by paediatricians with a special interest in growth and
skeletal diseaseii.

The theoretical concerns of growth impairment from bisphosphonates have
not been observed in the reported literature but there is a need to
perform more placebo-controlled clinical trialsi.

7j. Based
on evidence of increased growth rate versus some reported increased
fracture rate, growth hormone should probably not be used as
first-line therapy in osteogenesis imperfecta, pending further data
from clinical trials. Growth hormone for idiopathic juvenile
osteoporosis (which appears to improve naturally during puberty)
should currently be used only in research and not in clinical practicei.

i. Wright NM. Just
taller or more bone? The impact of growth hormone on osteogenesis
imperfecta and idiopathic juvenile osteoporosis. Journal of Pediatric
Endocrinology and Metabolism 2000; 13: 999-1002(Type V evidence – expert
review of three clinical trials (aggregate study population, 46) and 13
patient reports on osteogenesis imperfecta. No published reports were
found on idiopathic juvenile osteoporosis)

7k. Growth hormone
might be a useful adjunct in the treatment of severe growth retardation
and osteoporosis in children with juvenile chronic arthritis. The
longterm benefits of rhGH in the treatment of osteoporosis remain uncleari.Caveat: Small
and inconclusive study with a number of potential confounders (for
example, the control group used was from another study).

i. Rooney M, Davies
UM, Reeve J, Preece M, Ansell BM, Woo PMM. Bone mineral content and bone
mineral metabolism: changes after growth hormone treatment in juvenile
chronic arthritis. Journal of Rheumatology 2000; 27(4):
1073-1081(Type III evidence – bone
mineral content measurement in 20 children (of whom 17 were treated with
corticosteroid) before and after one year of rhGH. Children were
randomised to receive either low dose (12 IU/m2/week) or high
dose (24 IU/m2/week) rhGH. A non-treatment comparison group was
used from another study)